Project Summary/Abstract Walking is often impaired after a stroke, yet current rehabilitation strategies targeted towards walking fail to produce meaningful improvements in function. Our long-term research goal is to improve walking recovery following stroke. Lack of functional improvement may be attributable in part to the vast heterogeneity of sensorimotor impairments present in chronic stroke. However, this could also be due to a lack of biomarkers that adequately identify which individuals may respond to a given treatment. There is a critical need for non- invasive biomarkers that can predict walking ability and potential for recovery following stroke. This research plan proposes a functional biomarker that utilizes muscle stretch and electromyography (EMG) to quantify the health of neural circuitry that relates to walking and other lower extremity function. This biomarker, presence of the long-latency reflex (LLR), likely arises from the transcortical reflex pathway. The transcortical reflex is a polysynaptic reflex loop that is critical for integration of sensorimotor information. To evaluate the potential for LLR presence as a biomarker, the proposed research will demonstrate differences between healthy controls and individuals with chronic stroke while probing the health and short-term mutability of the sensory, integratory, and motor portions of the pathway. The specific aims are to: 1) characterize the cortical contribution of LLRs post-stroke and its relationship to lower extremity function, 2) assess the influence of stretch velocity and background activation on LLRs, and 3) to evaluate the effect of paired associative stimulation on LLRs. Through probing the sensory, supraspinal integratory, and motor components of the transcortical reflex pathway, we aim to gain a greater understanding of the locus of dysfunction in individuals with diminished or absent LLRs. Our overall hypothesis is that LLR dysfunction is derived from the transcortical reflex pathway, and that it is an important physiologic biomarker, identification of which will reduce the impact of heterogeneity observed in walking assessments post-stroke. Our preliminary work and the work of others indicates that some, but not all, individuals with chronic stroke have impairment in the transcortical reflex pathway. A dysfunctional transcortical reflex likely contributes to decreased functional scores and limited walking capacity in these individuals. The knowledge gained by performing these experiments will contribute to understanding dysfunctional motor physiology in persons following stroke. Future work will determine the capacity of LLRs for a priori prediction of treatment outcomes. The proposed characterization of task- dependent LLRs will lead to a clinically accessible biomarker for mutability of walking dysfunction post-stroke. This fellow and mentorship team are well-suited to achieve these aims and the knowledge gained will contribute to improving walking rehabilitation following stroke.